PROJECT SUMMARY/ABSTRACT Despite advancements in prevention and treatments for cardiovascular diseases (CVD), fiscal constraints have driven federal and state policymakers to make difficult choices among competing policy decisions, often without evidence of effectiveness. A comparative effectiveness approach, or in the absence of experimental data, a comparative assessment approach that compares the estimated impacts of modifying exposures using observational data, can critically inform this priority-setting process. We and others have demonstrated that social determinants, upstream social factors such as income inequality and social capital/cohesion, are key predictors of disease including CVD. Yet important questions remain about which social determinants have the biggest impacts on CVD burden. Furthermore, we lack knowledge on which subpopulations and states are most affected. In spite of calls for comparative assessments/effectiveness of strategies to improve population health and prevent CVD, including from NIH, we still lack knowledge on the relative CVD burden and economic impacts associated with modifying such factors. Given this information, there are critical needs to accurately estimate the impacts of social determinants on CVD risks; to translate these estimates into policy- setting tools including impacts on CVD burden and costs; and to compare and contrast the costs and sizes of these impacts. Our overall objective is to provide the first comparative assessment evidence base to compare the CVD burden and economic impacts of modifying key social determinants in middle-aged and older Americans. We will accomplish our overall objective by pursuing the following specific aims using data from two large, nationally-representative samples of middle-aged and older adults, the National Longitudinal Survey of Youths 1979 (NLSY) and the Health and Retirement Study (HRS), linked to social and economic measures by area of residence, and to Medicare claims and mortality databases: Aim #1) To determine which social determinants most strongly predict the risks of CVD incidence, mortality, and risk factors in middle-aged and older adults; Aim #2) To identify which subpopulations and geographic states are most vulnerable to the influences of social determinants on CVD burden and risk factors; and Aim #3) To determine which social determinants if modified are expected to yield the greatest reductions in CVD burden and its associated costs, both overall and by subpopulation. Regarding outcomes, our 3- year study is expected to identify the most promising social determinants on which to intervene to yield improvements in adult CVD burden. We will further establish how vulnerabilities to effects by geography and subpopulations may explain CVD disparities. By translating our estimates into population health and economic measures, we will directly respond to calls for comparative assessments and economic evaluations in CVD prevention research. Over the long term, we expect that our project will have high translational impact through guiding policymakers' evidence-based decisions to reduce CVD burden and inequities.